Cancer of the central nervous system (CNS), including the brain, meninges and spinal cord, ranks as the 12th most common malignancy diagnosed in men and the 15th most common in women, with 30% higher incidence in men. It is estimated that there will be 18,400 new cases and 12,690 deaths from brain and other nervous system tumors in the United States in 2004.[1] The combined incidence of primary invasive CNS tumors in that country is 6.6 per 100,000 persons per year, with an estimated mortality of 4.7.[2] Worldwide, approximately 176,000 new cases of brain and other CNS tumors were diagnosed in the year 2000, with an estimated mortality of 128,000.[3]
The pediatric situation is more bleak than that of adult CNS malignancy because of the higher incidence in that age group. CNS malignancies represent almost 17% of all malignancies during childhood according to United States data. CNS cancer as a group was the second most frequent malignancy of childhood and the most common of the solid tumors.
The seriousness and treatability of primary brain malignancies is determined by a number of variables including histology, size of tumor, extent of the malignancy, the patient's age and performance status, and the duration of symptoms.[4] Some primary brain tumors are curable by surgery alone, or by surgery and radiation therapy combined; but the remainder are not usually curable despite all the therapies combined.[5]
Further, while radiation therapy can be debilitating in adults, the use of radiation in treating pediatric brain tumors is not only technically demanding but more importantly, is debilitating in terms of growth and neurologic development.[6,7] Very young children with CNS cancer, especially infants with ependymoma or PNET, have low survival rates.
Alternative treatments for CNS malignancy are needed to provide new avenues of treatment.
PCT publication WO 00/69454 discloses the use of IGFBP-2 modulators to inhibit cancer.
PCT publication WO 00/78341 discloses a method for the prophylaxis and/or treatment of disorders related to insulin growth factor-I.
PCT publication WO 01/05435 describes a method for treating hormone-regulated tumors (for example, breast and prostatic tumors) by administration of an antisense oligodeoxynucleotide which is complementary to a portion of the gene encoding IGFBP-5.
PCT publication WO 02/22642 describes a method as provided for the treatment of prostate and other endocrine tumors by administration of an antisense oligodeoxynucleotide which is complementary to a portion of the gene encoding IGFBP-2.
U.S. published patent application US-2003-0158143-A1 describes the use of bispecific IGFBP-2/5 antisense oligonucleotides, especially for the treatment of endocrine-related tumors.
U.S. published patent application US 2003-0087857-A1 describes antisense modulation of IGFBP-5 expression